Leukemia inhibitory factor mediates cytokine-induced suppression of myenteric neurotransmitter release from rat intestine

Abstract

Background and Aims: Exposure of rat longitudinal muscle myenteric plexus to the proinflammatory cytokine interleukin (IL) 1β mimics the effects of nematode infection on enteric nerve function through a hitherto unidentified protein intermediate. It is postulated that leukemia inhibitory factor (LIF), the downstream intermediate of several IL-1-induced neuroimmune interactions, mediates IL-1β-induced suppression of acetylcholine release from rat jejunum. Methods: Preparations were preloaded with [3H]choline, and [3H]-acetylcholine release was induced by either electrical field stimulation or by 50 mmol/L KCI. Cytokines and anti-LIF antibodies were added to the preincubation media or to the superfusate before stimulation. Results: Human recombinant LIF had no immediate effects, but preincubation with the cytokine induced a concentration-dependent (2-100 ng/mL) and reversible suppression of acetylcholine release from rat longitudinal muscle myenteric plexus. The effects of human recombinant LIF on acetylcholine release were reversed by anti-human recombinant LIF-neutralizing antibody. Human recombinant IL-1β (10 ng/mL) induced a similar suppression of acetylcholine release, and the addition of anti-rat LIF antibody abolished the effects of exogenous IL-1 on acetylcholine release. Conclusions: IL-1β suppresses neurotransmitter release from rat myenteric plexus via the induction of LIF as a downstream intermediate.